Adjuvant therapy and recurrence risk in non-myoinvasive high-grade (stage IC) endometrial cancer: A systematic review and meta-analysis

Abstract

Objective: To summarize practice patterns and outcomes among patients with non-myoinvasive high-grade (formerly stage IA, now stage IC) endometrial cancer.

Methods: We conducted a systematic search using MEDLINE, Embase, Cochrane, Web of Science, and ClinicalTrials.gov databases from inception to May 8, 2024 to identify studies reporting on treatment and outcomes of non-myoinvasive high-grade endometrial cancer. We included full-text English reports of patients undergoing adjuvant therapy or surveillance for polyp- or endometrium-confined high-grade endometrial cancer without myometrial invasion containing data on recurrence or survival outcomes. Two reviewers independently screened studies; a third reviewer resolved disagreements. Data were extracted using a standardized form. The primary outcome was recurrence risk. Random-effects meta-analysis was used to summarize binomial proportions and to compare outcomes by adjuvant treatment strategy.

Results: A total of 29 studies were included, representing 2770 unique patients. Overall, 49.0 % of patients were managed with observation and 37.9 % with chemotherapy. Most patients (92.5 %) had serous histology. Of 23 studies with data on recurrence, 13.7 % of patients recurred, with a meta-analysis estimate recurrence risk of 11 % (95 % confidence interval [CI]: 8-15 %). Across 13 studies reporting on recurrence by receipt of chemotherapy versus no chemotherapy, comparative meta-analysis showed similar likelihood of recurrence (8.0 % versus 13.2 %; odds ratio 0.73, 95 % CI: 0.38-1.42). Comparative meta-analyses for (1) adjuvant therapy versus observation and (2) observation or vaginal brachytherapy versus chemotherapy and/or external beam radiation therapy demonstrated no statistically significant difference in recurrence risk. Sensitivity analyses results, including those limiting to studies of patients with serous histology (12 studies) or complete surgical staging (10 studies), were overall consistent with the primary analysis. Survival data was inconsistently reported and not amenable to meta-analysis.

Conclusion: Among patients with non-myoinvasive high-grade endometrial cancer, recurrence risk was 11 % and use of adjuvant therapy was not associated with reduced recurrence risk. Prospective study of this population is warranted.

Keywords: Adjuvant therapy; Non-myoinvasive high grade endometrial cancer; Overall survival; Recurrence risk; Systematic review; meta-analysis.